OBJECTIVES: A randomized phase III trial of Capecitabine/Cisplatin (XP) versus continuous infusion of 5-FU/Cisplatin (FP) as first-line therapy in patients with advanced gastric cancer (AGC) met its primary endpoint of non-inferior progression-free survival (PFS). There was a trend toward superior efficacy with XP in terms of both PFS and response rates. An economic assessment was conducted in Spain to compare the costs of both therapies considered unit costs and medical resource consumption for year 2007. METHODS: Direct medical costs were estimated from the Spanish National Healthcare System perspective. The therapies costs were estimated based on the clinical trial results on actual dose and the number of administrations, and unit costs in different hospitals in Spain. The adverse event (AE) profiles were used to estimate the costs of treating AEs. An expert panel estimated treatment patterns and costs of treating major AEs. Indirect costs for time and travel for drug administration were also estimated. RESULTS: Annual pharmacologic cost in the XP arm were estimated to be €1333 greater than in the XP arm, but drug administration costs and AE costs were lower in the XP arm (€2575 and €27, respectively). Overall, direct and indirect medical costs were estimated at €2688 in the XP arm and at €4014 in the FP arm. According to budget impact results, 1.58 patients are likely to be treated with XP for each patient treated with FP. CONCLUSIONS: In Spain, oral capecitabine reduce the number and time spent in infusion visits, and would produce significant direct medical cost savings in the treatment of patients with AGC. Given the trend to superior efficacy, the estimate direct and indirect cost savings, and the convenience of oral treatment, XP treatment would be considered less costly than FP treatment for AGC from both a health care system and a societal perspective.